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Dynamic expression of microRNAs in M2b polarized macrophages associated with systemic lupus erythematosus
Authors:Pengli Xiao  Chunsheng DongYan Yue  Sidong Xiong
Affiliation:Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, PR China
Abstract:Macrophage polarization contributes to the initiation and perpetuation of systemic lupus erythematosus (SLE). Our previous study demonstrated that M2b polarized macrophages induced by activated lymphocyte-derived DNA (ALD-DNA) have a crucial function in the initiation and progress of SLE disease. Accumulated data suggest that microRNAs (miRNAs) serve as critical regulators to control macrophage polarization. To investigate miRNA regulation during macrophage M2b polarization of SLE, miRNA microarrays of murine bone marrow derived macrophages (BMDMs) were performed following stimulation with ALD-DNA for 6 and 36 h. Over 11% of the 1111 analyzed miRNAs appeared differentially expressed during ALD-DNA triggered macrophage M2b polarization. Cluster analysis revealed certain patterns in miRNA expression that are closely linked to ALD-DNA induced macrophage M2b polarization. Analysis of the network structure showed that the predicted functions of the differentially regulated miRNAs at 6 h are significantly associated with inflammatory response and disease. Differentially regulated miRNAs identified at 36 h were determined to be significantly related to cell proliferation by biological network analysis. In this study, dynamic miRNA expression patterns and network analysis are described for the first time during ALD-DNA induced macrophage M2b polarization. The data not only provide a better understanding of miRNA-mediated macrophage polarization but also demonstrate the future therapeutic potential of targeting miRNAs in SLE patients.
Keywords:SLE, systemic lupus erythematosus   ALD-DNA, activated lymphocyte-derived DNA   UnALD-DNA, unactivated lymphocyte-derived DNA   BMDMs, murine bone marrow derived macrophages   miRNAs, microRNAs   PBMCs, peripheral blood mononuclear cells   FACS, fluorescence-activated cell sorting   MR, mannose receptor   qPCR, quantitative PCR   IPA, Ingenuity Pathways Analysis   GO, gene ontology   DAVID, Database for Annotation, Visualization, and Integrated Discovery   BP, biological process
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